ABSTRACT In this grant application, we propose to establish the University of Arizona Health Sciences ? Banner Health (UA-Banner) Healthcare Provider Organization (HPO) Enrollment Center for the primary purpose of recruiting the large majority (50-70%) of the American Indians/Alaska Natives (AI/AN) and Hispanics/Latinos (Hisp/Lat) participants required in the NIH Precision Medicine Initiative Cohort Program (PMI-CP) which will initially enroll one million participants. The PMI-CP is a timely development that will facilitate the ability to lever advances in genomics, metabolomics, and health technologies to reduce health disparities which are contributing to excessive suffering, disability, premature death, and economic losses particularly in racial/ethnic minority populations. Today, greater than 20 years after the NIH Revitalization Act, the goal of increasing the participation of minorities in biomedical research remains an unfulfilled dream with participation rates in clinical trials remaining at 0.2% for American Indian/Alaskan Native (AI/AN) and 1-2% for Hisp/Lat; far less than their 1.0% and 17.4% representations in the U.S. population, respectively. Without adequate representation of minorities in research studies, we will continue to practice ?Imprecise Medicine? in which research findings from studies conducted almost exclusively in non-Hispanic white populations are extrapolated to racial/ethnic minorities. The UA-Banner proposal is a formal partnership between the University of Arizona and Banner Health serving as the primary healthcare provider for 4.5 million individuals in seven Western States including 60% of the population of Arizona. We will utilize a well-defined potential participant pool of 1.725 million patients across 12 enrollment sites in Arizona, Alaska, and Wyoming to accomplish the following: (1) Enroll >150,000 volunteers, including 7,000 AI/AN, 90,000 Hisp/Lat and 53,000 non-Hispanic Whites, and individuals of other races/ethnicity into the PMI-CP; (2) Implement a comprehensive participant engagement plan that values the participants as ?partners in discovery? rather than ?research subjects?; (3) Use a secure and robust Enterprise Data Warehouse system to obtain, curate, de-identify, and normalize Electronic Health Records to transmit ?core datasets? quarterly to the Coordinating Center (CC) and provide ?subgroup? datasets for special studies; and (4) Collaborate with the CC, other HPOs, the participant technologies center, the PMI-CP Biobank, and the Steering Committee to develop and implement protocols and procedures, perform special studies, obtain additional specimens and increase the number and types of data collected. Our targeted enrollment of AI/AN and Hisp/Lat populations into the PMI-CP will bring us closer to one of the President's PMI goals - to reduce ethnic/racial health disparities in the U.S. through the robust participation of the AI/AN and Hisp/Lat populations in PMI-CP special research studies and novel clinical trials as a necessary step to realize the benefits of individualized therapies and tailored preventative strategies in racial/ethnic minority populations.